DOCSLIB.ORG

Unlocking the Body's Capacity for Self-Repair Engineer Biomedical

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Unlocking the Body's Capacity for Self-Repair Engineer Biomedical 4/16/2019 Healing from within: unlocking the body’s capacity for self-repair Brandon J. Tefft, Ph.D. Assistant Professor Engineer Biomedical Engineer http://topnews.in 1 4/16/2019 Regenerative Medicine http://apexbiologix.com Cells: Microscopic Tissue Engineers 131 million times per year Outline • Implantable medical devices • Regenerative medicine • Rapidly healing cardiovascular devices 2 4/16/2019 IMPLANTABLE MEDICAL DEVICES Top 10 in US Rank Device # per year in US $ per year in US 1 Artificial eye lenses 2,582,000 $8-10 billion 2 Ear tubes 715,000 $1-2 billion 3 Coronary stents 560,000 $7.5 billion 4 Artificial knees 543,000 $12 billion 5 Bone repair hardware 453,000 $4.5 billion 6 Intra-uterine devices 425,000 $340 million 7 Spinal fusion hardware 413,000 $10 billion 8 Breast implants 366,000 $992 million 9 Cardiac pacemakers 235,567 $4.5 billion 10 Artificial hips 230,000 $10.5 billion https://www.businessinsider.com Cardiac Pacemaker 1960 Today 3 4/16/2019 Artificial Hip 1962 Today Coronary Stent 1986 Today Cochlear Implant 1982 Today 4 4/16/2019 Coronary Bypass Graft 1955 Today Lessons from a Splinter https://www.tips-and-tricks.co REGENERATIVE MEDICINE 5 4/16/2019 Salamander Limb James Monaghan laboratory, Northeastern University Newborn Mouse Heart Science. 2011; 331(6020):1078-80 Regeneration in Humans http://thechart.blogs.cnn.com 6 4/16/2019 Heart Regeneration http://news.bbc.co.uk/2/hi/health/4904914.stm Early Days Science. 1993; 260(5110):920-6 Plast Reconstr Surg. 1997; 100(2):297-302 Cells Within Us • 200 types • 37 trillion cells • Stem cells http://www.equatorias.com/stem-cell-therapy-stem-cell-pluripotent-stem-cells/ 7 4/16/2019 Skin Arch Dermatol. 1999; 135(10):1219-22 Bladder https://www.newscientist.com Cardiovascular Tissues Humacyte Miromatrix Xeltis 8 4/16/2019 Musculoskeletal Tissues Bone Ligament Cartilage PLoS One. 2017; 12(6):e0179249 http://meeting.nesps.org/2011/47.cgi http://tuftsjournal.tufts.edu Nervous Tissues Peripheral Nerve Spinal Cord Prog Neurobiol. 2009; 89(3):231-9 PLoS One. 2015; 10(3):e0117709 RAPIDLY HEALING CARDIOVASCULAR DEVICES 9 4/16/2019 Coronary Stents www.adventisthealth.org Rapid Healing Magnetic Cell Capture FB US patent #8,465,453 B2 J Am Coll Cardiol. 2006;48(9):1839-45 10 4/16/2019 Magnetic Stents Ann Biomed Eng. 2014;42(12): 2416-24 J Vis Exp. 2015;103 Magnetic Nanoparticles Fe3O4 core (10 nm) PLGA-coated Fe3O4 (120 nm) J Vis Exp. 2015;105 Magnetic Cell Labeling Blood outgrowth endothelial cells Circ Res. 2003;93:1023-1025 IEEE Trans Magn. 2013;49(1):463-6 J Vis Exp. 2015;105 11 4/16/2019 In Vitro Cell Capture Tissue Engineering A. 2018;24(13-14):1157-1166 Rapid Healing in Pig Model Distal Middle Proximal Magnetic Magnetic Non-Magnetic Tissue Engineering A. 2018;24(13-14):1157-1166 Rapid Healing in Pig Model 316L stainless steel 2205 stainless steel (non-magnetic) (magnetic) Tissue Engineering A. 2018;24(13-14):1157-1166 12 4/16/2019 Rapid Healing in Pig Model 316L stainless steel 2205 stainless steel (non-magnetic) (magnetic) Tissue Engineering A. 2018;24(13-14):1157-1166 Rapid Healing in Pig Model 316L stainless steel 2205 stainless steel (non-magnetic) (magnetic) Tissue Engineering A. 2018;24(13-14):1157-1166 Rapidly Healing Vascular Grafts Non-magnetically cell seeded Magnetically cell seeded 13 4/16/2019 Rapid Healing Heart Valves Regenerative Medicine http://apexbiologix.com Acknowledgments • Medical College of Wisconsin • Marquette University • Mayo Clinic • National Institutes of Health 14.
Load more

Recommended publications
  • The Molecular Basis of Amphibian Limb Regeneration: Integrating the Old with the New David M
    seminars in CELL & DEVELOPMENTAL BIOLOGY, Vol. 13, 2002: pp. 345–352 doi:10.1016/S1084–9521(02)00090-3, available online at http://www.idealibrary.com on The molecular basis of amphibian limb regeneration: integrating the old with the new David M. Gardiner∗, Tetsuya Endo and Susan V. Bryant Is regeneration close to revealing its secrets? Rapid advances classical studies to guide the identification of the in technology and genomic information, coupled with several functions of this large set of genes. useful models to dissect regeneration, suggest that we soon The challenge of understanding the mechanisms may be in a position to encourage regeneration and enhanced controlling the biology of complex systems is hardly repair processes in humans. unique to regeneration biology. In recent years, techniques have become available to identify all the Key words: limb / regeneration / pattern formation / molecular components of a system, and to study the urodele / fibroblast / dedifferentiation / stem cells interactions between those components. Key to the success of such an approach is the ability to identify © 2002 Elsevier Science Ltd. All rights reserved. the molecules, while at the same time having an un- derstanding of the cell and tissue level properties of the system. The goal of this reviewis to discuss key insights from the classical literature as well as more recent molecular findings. We focus on three criti- Introduction cally important cell types: fibroblasts, epidermis and nerves. Each of these is necessary, and together they The study of amphibian limb regeneration has a rich are sufficient for the regeneration of a limb. Although experimental history.
    [Show full text]
  • The Legacy of Larval Infection on Immunological Dynamics Over Royalsocietypublishing.Org/Journal/Rstb Metamorphosis
    The legacy of larval infection on immunological dynamics over royalsocietypublishing.org/journal/rstb metamorphosis Justin T. Critchlow†, Adriana Norris† and Ann T. Tate Research Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA ATT, 0000-0001-6601-0234 Cite this article: Critchlow JT, Norris A, Tate AT. 2019 The legacy of larval infection on Insect metamorphosis promotes the exploration of different ecological niches, immunological dynamics over metamorphosis. as well as exposure to different parasites, across life stages. Adaptation should favour immune responses that are tailored to specific microbial threats, with Phil. Trans. R. Soc. B 374: 20190066. the potential for metamorphosis to decouple the underlying genetic or phys- http://dx.doi.org/10.1098/rstb.2019.0066 iological basis of immune responses in each stage. However, we do not have a good understanding of how early-life exposure to parasites influences Accepted: 16 May 2019 immune responses in subsequent life stages. Is there a developmental legacy of larval infection in holometabolous insect hosts? To address this question, we exposed flour beetle (Tribolium castaneum) larvae to a protozoan parasite ‘ One contribution of 13 to a theme issue The that inhabits the midgut of larvae and adults despite clearance during meta- evolution of complete metamorphosis’. morphosis. We quantified the expression of relevant immune genes in the gut and whole body of exposed and unexposed individuals during the Subject Areas: larval, pupal and adult stages. Our results suggest that parasite exposure induces the differential expression of several immune genes in the larval ecology, evolution, immunology stage that persist into subsequent stages. We also demonstrate that immune gene expression covariance is partially decoupled among tissues and life Keywords: stages.
    [Show full text]
  • Unveiling Mesenchymal Stromal Cells' Organizing Function in Regeneration Author List
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 16 January 2019 doi:10.20944/preprints201901.0161.v1 Peer-reviewed version available at Int. J. Mol. Sci. 2019, 20, 823; doi:10.3390/ijms20040823 1 Unveiling mesenchymal stromal cells’ organizing function in regeneration 2 3 Author list: 4 Peter P. Nimiritsky1,2 #, 5 Roman Yu. Eremichev1 #, 6 Natalia A. Alexandrushkina1,2 #, MD 7 Anastasia Yu. Efimenko1,2, MD, PhD 8 Vsevolod A. Tkachuk1-3, DSc 9 Pavel I. Makarevich* 1,2, MD, PhD 10 11 Author affiliations 12 1 – Institute for Regenerative Medicine, Medical research and education center, 13 Lomonosov Moscow State University, Moscow, Russia 14 2 – Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russia 15 3 – Laboratory of Molecular Endocrinology, National medical research center of 16 cardiology, Moscow, Russia 17 * corresponding author: [email protected] 18 # - equal contribution 19 20 1 © 2019 by the author(s). Distributed under a Creative Commons CC BY license. Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 16 January 2019 doi:10.20944/preprints201901.0161.v1 Peer-reviewed version available at Int. J. Mol. Sci. 2019, 20, 823; doi:10.3390/ijms20040823 21 Abstract 22 Regeneration is a fundamental process much attributed to functions of adult 23 stem cells. In last decades delivery of suspended adult stem cells is widely adopted 24 in regenerative medicine as a leading mean of cell therapy. However, adult stem 25 cells can not complete the task of human body regeneration effectively by 26 themselves as far as they need a receptive microenvironment (the niche) to engraft 27 and perform properly.
    [Show full text]
  • Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish
    International Journal of Molecular Sciences Article Pharmacological Enhancement of Regeneration-Dependent Regulatory T Cell Recruitment in Zebrafish Stephanie F. Zwi 1, Clarisse Choron 1, Dawei Zheng 2, David Nguyen 1, Yuxi Zhang 1, Camilla Roshal 1, Kazu Kikuchi 2,3,* and Daniel Hesselson 1,3,* 1 Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; [email protected] (S.F.Z.); [email protected] (C.C.); [email protected] (D.N.); [email protected] (Y.Z.); [email protected] (C.R.) 2 Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; [email protected] 3 St Vincent’s Clinical School, University of New South Wales, Kensington, NSW 2052, Australia * Correspondence: [email protected] (K.K.); [email protected] (D.H.) Received: 27 September 2019; Accepted: 15 October 2019; Published: 19 October 2019 Abstract: Regenerative capacity varies greatly between species. Mammals are limited in their ability to regenerate damaged cells, tissues and organs compared to organisms with robust regenerative responses, such as zebrafish. The regeneration of zebrafish tissues including the heart, spinal cord and retina requires foxp3a+ zebrafish regulatory T cells (zTregs). However, it remains unclear whether the muted regenerative responses in mammals are due to impaired recruitment and/or function of homologous mammalian regulatory T cell (Treg) populations. Here, we explore the possibility of enhancing zTreg recruitment with pharmacological interventions using the well-characterized zebrafish tail amputation model to establish a high-throughput screening platform. Injury-infiltrating zTregs were transgenically labelled to enable rapid quantification in live animals.
    [Show full text]
  • The Evolution of Regeneration – Where Does That Leave Mammals? MALCOLM MADEN*
    Int. J. Dev. Biol. 62: 369-372 (2018) https://doi.org/10.1387/ijdb.180031mm www.intjdevbiol.com The evolution of regeneration – where does that leave mammals? MALCOLM MADEN* Department of Biology & UF Genetics Institute, University of Florida, USA ABSTRACT This brief review considers the question of why some animals can regenerate and oth- ers cannot and elaborates the opposing views that have been expressed in the past on this topic, namely that regeneration is adaptive and has been gained or that it is a fundamental property of all organisms and has been lost. There is little empirical evidence to support either view, but some of the best comes from recent phylogenetic analyses of regenerative ability in Planarians which reveals that this property has been lost and gained several times in this group. In addition, a non- regenerating species has been induced to regenerate by altering only one signaling pathway. Ex- trapolating this to mammals it may be the case that there is more regenerative ability in mammals than has typically been thought to exist and that inducing regeneration in humans may not be as impossible as it may seem. The regenerative abilities of mammals is described and it turns out that there are several examples of classical epimorphic regeneration involving a blastema as exemplified by the regenerating Urodele limb that can be seen in mammals. Even the heart can regenerate in mammals which has long been considered to be a property unique to Urodeles and fish and several recent examples of regeneration have come from recent studies of the spiny mouse, Acomys, which are discussed here.
    [Show full text]
  • Regrowing Human Limbs
    MEDICINE Regrowing Human Limbs Progress on the road to regenerating major body parts, salamander-style, could transform the treatment of amputations and major wounds 56 SCIENTIFIC AMERICAN © 2008 SCIENTIFIC AMERICAN, INC. April 2008 Regrowing Human Limbs By Ken Muneoka, Manjong Han and David M. Gardiner salamander’s limbs are smaller and a of a salamander, but soon afterward the human bit slimier than those of most people, and amphibian wound-healing strategies diverge. Abut otherwise they are not that differ- Ours results in a scar and amounts to a failed ent from their human counterparts. The sala- regeneration response, but several signs indicate mander limb is encased in skin, and inside it is that humans do have the potential to rebuild composed of a bony skeleton, muscles, liga- complex parts. The key to making that happen ments, tendons, nerves and blood vessels. A will be tapping into our latent abilities so that loose arrangement of cells called fibroblasts our own wound healing becomes more salaman- holds all these internal tissues together and derlike. For this reason, our research first gives the limb its shape. focused on the experts to learn how it is done. Yet a salamander’s limb is unique in the world of vertebrates in that it can regrow from a stump Lessons from the Salamander after an amputation. An adult salamander can When the tiny salamander limb is amputated, regenerate a lost arm or leg this way over and blood vessels in the remaining stump contract over again, regardless of how many times the quickly, so bleeding is limited, and a layer of skin part is amputated.
    [Show full text]
  • Views Neuroscience, 4(9), 703–713
    Delayed Developmental Loss of Regeneration in Xenopus laevis tadpoles A thesis submitted to the Graduate School of the University of Cincinnati In partial fulfillment of the requirements for the degree of Master of Science In the department of Biological Sciences of the McMicken College of Arts and Sciences by Justin Y. He B.S. Biology, University of the Pacific Committee: Dr. Daniel Buchholz- Chair Dr. Ed Griff Dr. Josh Benoit March 2021 i Abstract: The prospect of spinal cord regeneration in humans is an exciting medical advance, but one that remains elusive from the complicated cellular and molecular mechanisms that prevent regeneration from happening. Various model organisms that do possess regenerative ability have been studied in hopes of understanding how spinal cord regeneration can be facilitated in humans. Recent studies in non-regenerative mammalian organisms however have uncovered the role of T3 signaling pathways in inhibiting regenerative capacity. These previous studies have shown inhibition of T3 in-vitro and in-vivo in various model organisms has increased the capacity for regeneration even in organisms that typically do not have such an ability. My dissertation provides a broad examination of previous literature exploring the barriers to regeneration in a wide range of model organisms, as well as potential therapeutic targets for inducing regeneration. Here, I also show how inhibition of T3 in X. laevis tadpoles allows for increased functional recovery from spinal cord transection. ii © Copyright by Justin He 2021 All Rights Reserved iii Acknowledgements As I conclude my studies at UC in the midst of the COVID-19 pandemic, thank you to all of my friends, colleagues, and family for their love and support in these hectic times.
    [Show full text]
  • Sierra F. and Kohanski R. (2013) Geroscience Offers a New Model For
    Public Policy & ® Aging Report Fall 2013 Volume 23, Number 4 The Longevity Dividend: Geroscience Meets Geropolitics ® Geroscience Offers a New Model for Investigating the Links Between Aging Biology and Susceptibility to Aging-Related Chronic Diseases Felipe Sierra • Ronald A. Kohanski The proportion of elders in the human population across the globe is higher than at any time in history, and improving and maintaining their health represent new frontiers of modern medicine. From the point of view of gerontologists, everyone who is in late life has experienced aging, the progressive decline of physical and mental abilities. Geriatricians, who study the diseases of older adults, stress that aging is itself the major risk factor for most of those diseases. Geroscientists, who research the underlying molecular and cellular processes of aging and age-related disease, believe that this basic biology of aging is the potential missing link between aging as the major risk factor and the chronic diseases prevalent in the older population. Accordingly, the Geroscience Interest Group (GSIG) at the National Institutes of Health (NIH) promotes innovative approaches to better understand the relationships between the biological processes of aging and age-related chronic diseases and disabilities. When the NIH was founded in 1930, the average human Since its inception, the NIH has responded to the life expectancy from birth was about 60 years in the United shifting landscape of health concerns and diseases by States (see, e.g., University of Oregon Mapping History establishing and reorganizing institutes and centers that are Project, n.d.). By the turn of the last century, life expectancy capable of responding forcefully both to widespread from birth had increased to about 77 years (see, e.g., diseases and to rare illnesses.
    [Show full text]
  • Pluripotent-Stem-Cell-Derived Hepatic Cells: Hepatocytes and Organoids for Liver Therapy and Regeneration
    cells Review Pluripotent-Stem-Cell-Derived Hepatic Cells: Hepatocytes and Organoids for Liver Therapy and Regeneration Antonietta Messina 1,2,3 , Eléanor Luce 1,2,3, Marwa Hussein 1,2,3 and Anne Dubart-Kupperschmitt 1,2,3,* 1 INSERM unité mixte de recherche (UMR_S) 1193, F-94800 Villejuif, France; [email protected] (A.M.); [email protected] (E.L.); [email protected] (M.H.) 2 UMR_S 1193, Université Paris-Sud/Paris-Saclay, F-94800 Villejuif, France 3 Département Hospitalo-Universitaire (DHU) Hépatinov, F-94800 Villejuif, France * Correspondence: [email protected]; Tel.: +33-145595138 Received: 30 November 2019; Accepted: 10 February 2020; Published: 12 February 2020 Abstract: The liver is a very complex organ that ensures numerous functions; it is thus susceptible to multiple types of damage and dysfunction. Since 1983, orthotopic liver transplantation (OLT) has been considered the only medical solution available to patients when most of their liver function is lost. Unfortunately, the number of patients waiting for OLT is worryingly increasing, and extracorporeal liver support devices are not yet able to counteract the problem. In this review, the current and expected methodologies in liver regeneration are briefly analyzed. In particular, human pluripotent stem cells (hPSCs) as a source of hepatic cells for liver therapy and regeneration are discussed. Principles of hPSC differentiation into hepatocytes are explored, along with the current limitations that have led to the development of 3D culture systems and organoid production. Expected applications of these organoids are discussed with particular attention paid to bio artificial liver (BAL) devices and liver bio-fabrication.
    [Show full text]
  • Limb Regeneration in Humans: Micromanaging a Plastic Environment
    ENGINEERING AND NATURAL SCIENCES Limb Regeneration in Humans: Micromanaging a Plastic Environment Sarah Dunk College of Arts and Science, Vanderbilt University A popular topic as of late, stem cell research has intrigued many with its remarkable potential in the realm of human health. Multipotent stem cells have been found throughout the entire human body, indicating that adult tissues may be able to repair and regenerate themselves. Although organs such as the heart, liver, or lungs do not currently regenerate in humans, the presence of these somatic stem cells indicates that we possess the necessary structures to do so. By studying the axolotl, a species of salamander known to effectively regenerate limbs and organs, scientists have come closer to understanding human regeneration. After various studies performed on the axolotl, results have indicated that limb regeneration occurs in a step-wise fashion, in which certain qualifications must be met to progress to the next step. This is groundbreaking because the lack of human regeneration can be attributed to the absence of a correct preliminary envi- ronment, not in our sheer inability to do so. If we can determine the factors that influence each individual step of limb regeneration, we could theoretically micromanage regenerating environ- ments to provide the exact outcome we desire. In the last century, stem cell research has sparked model system for limb regeneration”, which highlights a widespread interest in modern science. Stem cells are the important and necessary steps in initiating regenera- remarkable in their ability to develop into many differ- tion. However, instead of examining “normal” regen- ent types of cells throughout development, indicating eration, the study induced ectopic (out of place) limbs they potentially provide benefits for human health.
    [Show full text]
  • BREAKTHROUGHS in BIOSCIENCE/ ADVISORY COMMITTEE REGENERATIVE MEDICINE CHAIR» AUTHOR» Paula H
    / FALL 2016 Regenerative Medicine Advances from the Convergence of Biology & Engineering WHAT'S INSIDE » EXCEPTIONAL REGENERATION IN NATURE 2 / NATURAL REGENERATION IN HUMAN TISSUES 3 TISSUE ENGINEERING 4 / CONSTRUCTING SKIN 7 / TUBULAR ORGANS 8 / BONE ENGINEERING 8 MENDING BROKEN HEARTS 8 / REAWAKENING THE HUMAN HEART 10 / THE ROAD AHEAD 11 BREAKTHROUGHS IN BIOSCIENCE/ ADVISORY COMMITTEE REGENERATIVE MEDICINE CHAIR» AUTHOR» Paula H. Stern, PhD Cathryn M. Delude, of Santa Fe, New Mexico, writes about Northwestern University Feinberg School of Medicine science and medicine for magazines, newspapers, and COMMITTEE MEMBERS» research institutes. Her articles have appeared in Nature Aditi Bhargava, PhD Outlook, The Journal of the National Cancer Association University of California, San Francisco (JNCI), AACR’s Cancer Discovery, Proto: Dispatches from David L. Brautigan, PhD the Frontiers of Medicine, Los Angeles Times, Boston Globe, University of Virginia School of Medicine New York Times, Scientific American, and The Scientist. She has also written for the Howard Hughes Medical Institute, David B. Burr, PhD Harvard Health Publications, Harvard School of Public Health, Indiana University School of Medicine Massachusetts General Hospital, Massachusetts Institute of Blanche Capel, PhD Technology, Dana Farber Cancer Center, Stowers Institute Duke University Medical Center for Medical Research, and the National Institutes of Health Rao L. Divi, PhD Office of Science Education. This is her fifth article in FASEB’s National Cancer Institute, National Institutes of Health Breakthroughs in Bioscience series. Marnie Halpern, PhD SCIENTIFIC ADVISOR» Carnegie Institution for Science Henry J. Donahue, PhD is the School of Engineering Foun- dation Professor and Chair of the Department of Biomedical Loraine Oman-Ganes, MD, FRCP(C), CCMG, FACMG Engineering at the Virginia Commonwealth University.
    [Show full text]
  • Limb Regeneration in Axolotl: Is It Superhealing?
    Review Article Limb and Fin Regeneration TheScientificWorldJOURNAL (2006), 6(S1), 12-25 TSW Development & Embryology ISSN 1537-744X; DOI 10.1100/tsw.2006.113 Limb Regeneration in Axolotl: Is It Superhealing? Stéphane Roy* and Mathieu Lévesque Department of Stomatology, Faculty of Dentistry, Université de Montréal, C.P. 6128 succursale Centre-ville Montréal, Québec Canada H3C 3J7 E-mails: [email protected]; [email protected] Received February 28, 2006; Revised April 12, 2006; Accepted April 28, 2006; Published May 5, 2006 The ability of axolotls to regenerate their limbs is almost legendary. In fact, urodeles such as the axolotl are the only vertebrates that can regenerate multiple structures like their limbs, jaws, tail, spinal cord, and skin (the list goes on) throughout their lives. It is therefore surprising to realize, although we have known of their regenerative potential for over 200 years, how little we understand the mechanisms behind this achievement of adult tissue morphogenesis. Many observations can be drawn between regeneration and other disciplines such as development and wound healing. In this review, we present new developments in functional analysis that will help to address the role of specific genes during the process of regeneration. We also present an analysis of the resemblance between wound healing and regeneration, and discuss whether axolotls are superhealers. A better understanding of these animals’ regenerative capacity could lead to major benefits by providing regenerative medicine with directions on how to develop therapeutic approaches leading to regeneration in humans. KEYWORDS: axolotl, urodele, limb, regeneration, wound healing, functional analysis, amphibians INTRODUCTION Regenerative medicine is an emerging field of medical research that promises to unlock the secrets of how the body can regenerate itself.
    [Show full text]